Cell Genesys, Inc. (CEGE)

[acgood]

CEGE- GVAX ASCO abstracts...
Conclusion: It just didn't work.

VITAL1:
http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=64&abstractID=20543

Background: A phase III trial comparing GVAX immunotherapy (CG1940/CG8711) to docetaxel plus prednisone was initiated in 2004. The study was designed to enroll 600 patients (pts) with a primary endpoint of superiority in overall survival. It was conducted at over 100 centers in North America and the European Union. The study was prematurely terminated based on the results of a previously unplanned futility analysis conducted by the study's independent Data Monitoring Committee (IDMC) which determined that the study had less than a 30% chance of meeting its predefined primary endpoint of improvement in overall survival. Methods: Castration-resistant, chemotherapy-naïve men without cancer-related pain requiring opioid analgesics were eligible. CG1940/CG8711 (500 million cells prime/300 million cells boost doses q 2 wks x 13 doses) was administered in the experimental arm (G) followed by maintenance GVAX immunotherapy (q 4 wks). Docetaxel (75mg/m2 q 3 wks x 9 cycles) plus prednisone (10 mg daily) was given in the control arm (D+P). Results: The study completed accrual of 626 patients in 2007, and all completed the initial 6 month treatment period. At the time of study termination the median follow-up was 66 weeks. Analysis of the dataset revealed no imbalance in patient baseline characteristics. The Halabi predicted survival (HPS) was 16 months for each arm. More than 45% of pts enrolled were Gleason > 8. The median number of doses was 8 (range 1-51) for G and 9 (1-16) for D+P. Grade 3 or higher related adverse events were 8.8% on G versus 43% on D+P. The median survival was 20.7 months on G and 21.7 months on D+P, hazard ratio 1.03, 95% CI (0.83, 1.28), p=0.78, stratified log-rank test. The Kaplan-Meier (KM) curve shows G crossing above D+P at approximately 22 months. In the subset of men with HPS > 18 months (n=264) median survival was prolonged on G (29.7 months) compared to D+P (27.1 months), HR 0.90 (0.61-1.33), p=0.60.Conclusions: This randomized phase III trial shows that the toxicity profile of GVAX is favorable compared to D+P. While survival was not significantly improved overall compared to chemotherapy, a late favorable effect of GVAX is suggested by crossover in the KM survival curve. Pts with HPS >= 18mo may have a more favorable response to immunotherapy.

VITAL2:
http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=64&abstractID=20295

A phase III trial of GVAX immunotherapy for prostate cancer in combination with docetaxel versus docetaxel plus prednisone in symptomatic, castration-resistant prostate cancer (CRPC)

ntroduction: A phase III trial comparing GVAX immunotherapy for prostate cancer in combination with docetaxel to docetaxel plus prednisone was initiated in 2005. The study was designed to enroll 600 patients (pts) with a primary endpoint of superiority in overall survival. It was conducted at over 100 centers in North America and the European Union. Methods: Pts with taxane-naïve CRPC with pain requiring opioid analgesics were eligible. Docetaxel (75 mg/m2 q 3 wks x 10 cycles) was given in both arms. Prednisone (10 mg daily) was given in the control arm (D+P). CG1940/CG8711 (500 million cells prime/300 million cells boost doses q 3 wks x 10 cycles) was administered 2 days following each docetaxel infusion in the experimental arm (D+G) followed by maintenance immunotherapy alone (q 4 wks). Results: The study was prematurely terminated after accrual of 408 pts due to an imbalance in deaths, with 67 deaths in the D+G arm and 47 deaths in the D+P arm. The preliminary analysis revealed no imbalance in pt baseline characteristics. Median predicted survival based on the Halabi prognostic factor nomogram was 13 months in both arms. Fewer cycles of docetaxel were received in the D+G arm (median of 5 vs. 7, p = 0.0100, Wilcoxon Rank-Sum test). Fewer pts in the D+G arm completed all 10 cycles (27 vs. 37 percent, p = 0.0116, chi-square test). No significant toxicities in the D+G arm were observed that could explain the imbalance in deaths. 85% of deaths were reported as due to prostate cancer in both arms. The imbalance was restricted to deaths from prostate cancer and to pts with evidence of PSA progression at time of death. Overall survival was shorter in the D+G arm with median survival of 12.2 months, vs. 14.1 months in the D+P arm (hazard ratio 1.70, 95% CI [1.15, 2.53], p = 0.0076 per stratified log-rank test). Conclusions: Preliminary analysis of this prematurely terminated trial demonstrated a survival advantage for the control arm, D+P over the experimental arm D+G. No unexpected safety issues were identified. Exploratory analyses to identify subgroups of pts with preferential benefit from the investigational therapy are underway.